Dermal Cell News Volume 5.15 | Apr 29 2019

TOP STORY

Adaptive Immune Resistance Emerges from Tumor-Initiating Stem Cells

Researchers designed a skin cancer model for squamous cell carcinoma that could be effectively challenged by adoptive cytotoxic T cell transfer (ACT)-based immunotherapy. Using single-cell RNA sequencing and lineage tracing, they found that transforming growth factor β-responding tumor-initiating stem cells were superior at resisting ACT and formed the root of tumor relapse. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Human Skin Long Noncoding RNA WAKMAR1 Regulates Wound Healing by Enhancing Keratinocyte Migration

Scientists characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated long noncoding RNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. [Proc Natl Acad Sci USA] Full Article

Myeloid Cell-Specific Sirtuin 6 Deficiency Delays Wound Healing in Mice by Modulating Inflammation and Macrophage Phenotypes

Consistent with the in vivo wound closure defects observed in knockout (KO) mice, keratinocytes and fibroblasts treated with KO macrophage-derived conditioned medium migrated slower than those treated with wild-type macrophage-derived conditioned medium. [Exp Mol Med] Full Article

Elafibranor Restricts Lipogenic and Inflammatory Responses in a Human Skin Stem Cell-Derived Model of NASH

Exposure of cells to lipogenic and pro-inflammatory factors resulted in a characteristic non-alcoholic steatohepatitis (NASH) response, as indicated by intracellular lipid accumulation, modulation of NASH-specific gene expression, increased caspase-3/7 activity and the secretion of inflammatory markers. [Pharmacol Res] Abstract | Graphical Abstract

OVOL2 Induces Mesenchymal-to-Epithelial Transition in Fibroblasts and Enhances Cell-State Reprogramming towards Epithelial Lineages

Scientists identified the transcription factors that efficiently induced mesenchymal-to-epithelial transition in dermal fibroblasts. In TP63/KLF4-induced keratinocyte-like cell-state reprogramming, OVOL2 greatly facilitated the activation of epithelial and keratinocyte-specific genes. [Sci Rep] Full Article

Senescent Dermal Fibroblasts Negatively Influence Fibroblast Extracellular Matrix-Related Gene Expression Partly via Secretion of Complement Factor D

Researchers cocultured dermal young fibroblasts with senescent cells in Transwells, in which two cell types were separated by a semipermeable membrane. Young fibroblasts in coculture showed decreased collagen type I alpha 1 chain and elastin gene expression, and increased matrix metalloproteinase 1 gene expression. [BioFactors] Full Article

SKIN CANCERS & DISORDERS

BCL-XL and MCL-1 Are the Key BCL-2 Family Proteins in Melanoma Cell Survival

Investigators tested a panel of established and early passage patient-derived cell lines against several BH3-mimetic drugs designed to target individual or subsets of pro-survival BCL-2 proteins, alone and in combination, in both 2D and 3D cell cultures. [Cell Death Dis] Full Article

Rbfox2 Dissociation from Stress Granules Suppresses Cancer Progression

Resveratrol treatment inhibited stress granule-mediated RNA-binding protein fox-1 homolog 2 (Rbfox2) localization, further inhibiting retinoblastoma 1 protein expression, and inhibited specific Rbfox2 localization to the cytoplasm in melanoma B16-F10 cells, thereby effectively inhibiting metastasis and tumor growth ability. [Exp Mol Med] Full Article

Structural and Functional Characterization of β₂-Glycoprotein I Domain 1 in Anti-Melanoma Cell Migration

Researchers found that purified β₂-glycoprotein I as well as recombinant β₂-glycoprotein I full-length, polypeptide domains I-IV, and polypeptide domain I significantly inhibited melanoma cell migration, proliferation and invasion. [Cancer Sci] Abstract

The Synthetic Flavagline FL3 Spares Normal Human Skin Cells from Its Cytotoxic Effect via an Activation of Bad

Investigators provided the underlying molecular events by which normal skin cells remain unaffected after exposure to the synthetic flavagline FL3. The anticancer agent failed to trigger apoptosis of healthy cells and was unable to induce the depolarization of their mitochondrial membrane and the cytosolic release of cytochrome C, in contrast to what was observed for cancer cells. [Toxicol in Vitro] Abstract | Graphical Abstract

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T Cell Pathology in Skin Inflammation

The authors show how the increasing knowledge of T cell biology has been comprehensively translated into the pathogenetic understanding of respective model skin diseases and has revolutionized their daily clinical management. [Semin Immunopathol] Full Article

The Impact of Recent Advances in Lipidomics and Redox Lipidomics on Dermatological Research

Novel lipidomic techniques have been applied to study systemic and topical lipid abnormalities in patient cohorts. Studies have refined the knowledge on eicosanoid signaling in both diseases, and have identified novel biomarkers and potential disease mediators. [Free Radic Biol Med] Abstract

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Krystal Biotech Announces Five Presentations of Clinical and Preclinical Data

Krystal Biotech Inc. has announced presentations of clinical data for KB103 to treat dystrophic epidermolysis bullosa, and preclinical data on KB105 for the treatment of autosomal recessive congenital ichthyosis and KB104 for the treatment of Netherton syndrome. [Press release from Krystal Biotech, Inc. discussing research to be presented at the Society for Investigative Dermatology (SID) 77^th Annual Meeting, Chicago] Press Release

Foamix to Present Late Breaking Data

Foamix Pharmaceuticals Ltd. announced it will present two late-breaking posters relating to its topical product candidate FMX101, a 4% minocycline foam being developed for the treatment of moderate-to-severe acne. [Press release from Foamix Pharmaceuticals Ltd. discussing research to be presented at the Society for Investigative Dermatology (SID) 77^th Annual Meeting, Chicago] Press Release

SkinTE Clinical Data to be Presented, PolarityTE to Host Booth and SkinTE Event

PolarityTE, Inc. announced that new clinical data on the use of its SkinTE™ product will be presented. [Press release from PolarityTE, Inc. discussing research to be presented at the Symposium on Advanced Wound Care (SAWC) Spring, Wound Healing Society (WHS) Meeting, San Antonio] Press Release

CHMP Issues Positive Opinion for Libtayo^® (Cemiplimab) in Advanced Cutaneous Squamous Cell Carcinoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorization of cemiplimab. The CHMP recommended its conditional approval for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation. [Sanofi] Press Release

Vyome Therapeutics Begins Dosing in Phase II Trial of VB-1953 in Moderate to Severe Inflammatory Acne Vulgaris

Vyome Therapeutics Inc. announced that it has dosed the first patient in its Phase II trial of the company’s lead clinical candidate, VB-1953, for the treatment of moderate to severe inflammatory acne vulgaris. [Vyome Therapeutics, Inc. (GlobeNewswire, Inc.)] Press Release

Akari Therapeutics Announces Positive Initial Phase II Clinical Data in Orphan Skin Disease Bullous Pemphigoid

Akari Therapeutics plc has announced positive initial Phase II clinical data from the first three bullous pemphigoid patients in an ongoing clinical trial. [Akari Therapeutics plc] Press Release

UCI to Establish Skin Biology, Diseases Resource Center with $4 Million NIH Award

With nearly $4 million in funding from the National Institute of Arthritis & Musculoskeletal & Skin Diseases, the University of California, Irvine (UCI) will establish the UCI Skin Biology Resource-based Center. One of only six such sites in the nation, it will provide critical research infrastructure, shared facilities, services and resources to groups of investigators studying skin biology and diseases. [University of California, Irvine] Press Release

US Universities Reassess Collaborations with Foreign Scientists in Wake of NIH Letters

Kuspa’s attempt to stay ahead of the US National Institutes of Health (NIH) came to naught. A few months into the audit, Baylor College of Medicine received letters from the NIH asking about four scientists it believed had violated the agency’s rule requiring them to disclose all foreign ties relating to their research. [ScienceInsider] Editorial

Elsevier and Norway Agree on New Open-Access Deal

After unsuccessful negotiations between a coalition of Norwegian organizations and the academic publisher Elsevier culminated in canceled subscriptions earlier this year, the two have successfully established a new nationwide licensing agreement. [The Scientist] Editorial

NEW Keystone Symposia: Single Cell Biology: Pushing New Frontiers in the Life Sciences
May 4-8, 2020
Florence, Italy

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NEW Faculty Positions – Skin Cancer (Columbia University)

Postdoctoral Research Position – Molecular Biology & Cancer Research (Augusta University)

Postdoctoral Fellowship – Cancer Biology (University of Miami)

Research Assistant – Melanoma Medical Oncology (MD Anderson Cancer Center)

Postdoctoral Fellowship – Epidermal Stem Cell Research (University of California, San Diego)

Postdoctoral Fellowship – Immune Cell-Mediated Regulation (Hospital for Special Surgery)

Postdoctoral Researcher – Skin Biology (University of Wisconsin-Madison)

Director – Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health)

Research Assistant – Burn Research (Sunnybrook Health Sciences Centre)

PhD Position – Epidermal Tissue Mechanics (Forschungszentrum Jülich)

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